bortezomib in treating children with advanced solid tumors

Conditions: Unspecified Childhood Solid Tumor, Protocol Specific

Summary: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. phase i trial to study the effectiveness of bortezomib in treating children who have advanced solid tumors that have not responded to previous treatment.

primary objectives: i. determine the maximum tolerated dose of bortezomib in pediatric patients with refractory solid tumors. ii. determine the dose-limiting toxicity and other toxic effects of this regimen in these patients. iii. preliminarily determine the antitumor activity of this regimen in these patients. outline: this is a dose-escalation study. patients receive bortezomib iv on days 1, 4, 8, and 11. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. if dose-limiting toxicity in the form of myelosuppression occurs in stratum i, dose escalation continues with patients meeting the qualifications for stratum ii. projected accrual: approximately 24-36 patients will be accrued for this study.

Eligibility criteria:
inclusion criteria: * histologically confirmed solid tumor that is refractory to standard therapy or for which no standard therapy exists * histologic confirmation not required for brainstem glioma or optic pathway tumor * ineligible for therapies of higher priority * stratum ii only: * no bone marrow involvement * performance status - karnofsky 50-100% (over 10 years of age) * performance status - lansky 50-100% (10 years of age and under) * at least 8 weeks * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 75,000/mm\^3 (transfusion independent) * hemoglobin at least 8 g/dl (rbc transfusions allowed) * bilirubin less than 1.5 mg/dl * alt less than 5 times normal for age * albumin at least 2 g/dl * creatinine no greater than upper limit of normal for age * creatinine clearance or radioisotope glomerular filtration rate greater than 70 ml/min * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * neurologic deficits related to cns tumors allowed if relatively stable for at least 2 weeks * no uncontrolled infection * at least 7 days since prior biologic therapy and recovered * at least 3 months since prior allogeneic stem cell transplantation * at least 1 week since prior growth factors * stratum ii only: * no prior stem cell transplantation with or without total body irradiation * at least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered * stratum ii only: * no more than 2 prior multi-agent chemotherapy regimens * more than 2 single-agent regimens allowed * concurrent dexamethasone allowed for cns tumors if stable dose for at least 2 weeks * see biologic therapy * at least 2 weeks since prior palliative local radiotherapy * at least 6 months since prior craniospinal radiotherapy or radiotherapy to at least 50% of pelvis * at least 6 weeks since prior substantial bone marrow radiotherapy * recovered from prior radiotherapy * stratum ii only: * no prior radiotherapy to more than 20% of bone marrow * no prior bortezomib * no concurrent anticonvulsants * no other concurrent investigational agents